Use of a protease inhibitor with two nucleoside antiretroviral agents (NRTIs) has become the standard of care for treatment of many HIV-infected adults and children. Combination therapy with two protease inhibitors is currently under investigation in HIV-infected adults and children. Saquinavir-hard gelatin capsule (SQV-HGC) was the first HIV protease inhibitor approved for use in adults by the U.S. Food and Drug Administration. Recently, a new formulation of saquinavir, saquinavir-soft gelatin capsule (SQV-SGC), has been studied in adults and children. SQV-SGC appears to be a promising agent for inclusion in pediatric HIV combination therapy regimens. The drug may have advantages over other protease inhibitors in terms of tolerability and safety. Favorable pharmacologic interactions between saquinavir and either nelfinavir or ritonavir may enhance antiviral effect. Cross-resistance between saquinavir and other protease inhibitors is uncommon, suggesting possible utility of the drug even in patients who have failed therapy with other protease inhibitors. This is a 48 week, multi-center, two-arm, randomized, open label study of two combination therapy regimens in HIV-infected children aged 3 to 16. The primary objective of the study is to assess the tolerance and safety of orally administered SQV-SGC, given in combination with two NRTIs, or orally administered SQV-SGC and nelfinavir and 1 or 2 NRTIs in HIV infected children.